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A Prospective Trial of Enavogliflozin to Evaluate Cardio-renal Outcome in Type 2 Diabetes Mellitus Patients

Phase 4
Recruiting
Conditions
Diabetes Mellitus, Type 2
Cardiovascular Diseases
Kidney Diseases
Interventions
Registration Number
NCT06642623
Lead Sponsor
Yonsei University
Brief Summary

The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor, enavogliflozin, effectively reduces glycated hemoglobin (HbA1c) levels and body weight without increasing the risk of serious adverse events. However, its long-term clinical benefits concerning cardiovascular and renal outcomes have yet to be thoroughly studied. This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults aged 19 or older with type 2 diabetes who have a history of, or are at risk for, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular and renal events. This trial aims to determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with type 2 diabetes and cardiovascular risk factors. It will also clarify role of enavogliflozin in preventing vascular complications in this patient population.

Detailed Description

The ENVELOP study aims to assess cardiorenal outcomes following enavogliflozin administration compared with dapagliflozin or empagliflozin in Korean patients with type 2 diabetes, representing the first large-scale SGLT2 inhibitor outcome study targeting this population.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
2862
Inclusion Criteria
  1. Male and female adults aged 19 years and older at screening
  2. Subjects diagnosed with T2D at screening
  3. Subjects on treatment with or requiring treatment with enavogliflozin, dapagliflozin, or empagliflozin within the scope of label and reimbursement criteria
Exclusion Criteria
  1. Subjects with different types of diabetes mellitus other than T2D
  2. Subjects with moderate to severe hepatic impairment
  3. Subjects with contraindications to SGLT-2 inhibitors, i.e., kidney function disorders with estimated glomerular filtration (eGFR) <60 mL/min/1.73 m2, end stage renal disease (ESRD), or on dialysis
  4. Subjects with major comorbidities
  5. Subjects with a history of hypersensitivity to enavogliflozin, dapagliflozin, or empagliflozin and any of its components
  6. Pregnant or breastfeeding women

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Enavogliflozin GroupEnavogliflozinSubjects will take Enavogliflozin according to the investigator's judgment.
Dapagliflozin, Empagliflozin GroupDapagliflozin or EmpagliflozinSubjects will take Dapagliflozin or Empagliflozin according to the investigator's judgment.
Primary Outcome Measures
NameTimeMethod
Time from randomization to first onset of cardiorenal composite outcome event6 months, 12 months, 24 months, 36 months and 48 month

Major adverse cardiovascular events include nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalization for unstable angina, hospitalization for heart failure, coronary or peripheral revascularization, and death from any cause. Renal events include a sustained decline in estimated glomerular filtration rate (GFR) calculated by means of the Chronic Kidney Disease Epidemiology Collaboration equation of ≥40% from baseline to \<60 mL/min/1.73m2, onset of end-stage kidney disease (dialysis for ≥28 days, kidney transplantation, or an estimated GFR of \<15 mL/min/1.73m2), development of macroalbuminuria, and death from renal causes.

Secondary Outcome Measures
NameTimeMethod
major renal events6 months, 12 months, 24 months, 36 months and 48 months

Time to first event of a composite of major kidney events

progression of macroalbuminuria6 months, 12 months, 24 months, 36 months and 48 months

Time to development of macroalbuminuria

coronary or peripheral revascularization6 months, 12 months, 24 months, 36 months and 48 months

Time to first event of coronary or peripheral revascularization

Time from randomization to the first onset of 3-point MACE and proportion of the patients6 months, 12 months, 24 months, 36 months and 48 months

Time to first event of a composite of key major adverse cardiovascular events (non-fatal MI, non-fatal stroke, and death from cardiovascular causes)

death from any cause6 months, 12 months, 24 months, 36 months and 48 months

Time to death from any cause

death from cardiovascular causes6 months, 12 months, 24 months, 36 months and 48 months

Time to death from cardiovascular cause

hospitalization due to unstable angina6 months, 12 months, 24 months, 36 months and 48 months

Time to first event of hospitalization due to unstable angina

hospitalization due to heart failure6 months, 12 months, 24 months, 36 months and 48 months

Time to first event of hospitalization due to heart failure

Trial Locations

Locations (1)

Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea

🇰🇷

Seoul, Korea, Republic of

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